Portal hypertension evolving from sickled hepatopathy: Could hepatic venous Doppler ultrasound be beneficial in its evaluation?

PURPOSE: Sickle cell intrahepatic cholestasis involves sickling within hepatic sinusoids leading to vascular stasis and localized hypoxia resulting in ballooning of the hepatocytes causing a direct back pressure effect with resultant intracanalicular cholestasis. Vascular stasis may ultimately lead to portal hypertension. We proposed to document findings suggestive of portal hypertension evolving from hepatopathy in steady-state sickle cell disease (SCD) patients using hepatic venous Doppler ultrasound. METHODS: This is a prospective case series of 6 SCD subjects in steady-state (median age, 30 years; range, 19-43), comprising of 3 males and 3 females, who underwent a routine Doppler ultrasound evaluation of their hepatic veins and were discovered to have an abnormal biphasic waveform pattern. Venous blood was obtained from all subjects to evaluate for P-selectin, homocysteine, foetal haemoglobin, haematocrit levels, white cell and platelet counts. Doppler ultrasound was also carried out on all subjects to evaluate for the hepatic waveform, right renal artery RI and PI along with the hepatic artery velocities. RESULTS: All the 6 subjects had reduced haematocrit (median value of 21.5%; range, 18-25%) and some degree of renal dysfunction (plasma cystatin-C ranged from 1.6 to 12.2 mg/L). Elevated white cell count, hyperhomocysteinemia, reduced SpO2(<94.0%) and reduced estimated GFR (eGFR < 90 ml/min) was also noted in 4 subjects (66.7%). Similarly, 4 subjects (66.7%) had elevated RI in the right kidneys while 3 subjects (50.0%) had elevated PI in the right kidney. CONCLUSION: Doppler ultrasound Hepatic vein waveform analysis may be a useful examination in the evaluation of patients with SCD as it may elicit feature of portal hypertension. Further studies are suggested to confirm this in a larger population of SCD patients using the gold standard.

Challenges to Care and Medication Adherence of Patients With Chronic Myeloid Leukemia in a Resource Limited Setting: A Qualitative Study.

The factors related to care of patients with chronic myeloid leukemia (CML) often affects treatment outcome. We examined adherence to medication and other challenges to care in our patients on treatment of CML. This qualitative study involved in-depth interviews of 20 patients with CML receiving free imatinib (Glivec) from the Glivec International Patients' Assistance Program. Data collected were thematically analyzed. Findings revealed that despite free drug assistance, there was relative lack of awareness resulting in inappropriate health-seeking behavior. The challenges cut across situations such as poverty, fear of the sustenance of the compassionate drug program, and living far away from the clinic. Forgetfulness was reported as the cause of poor adherence in this study. Suggested solutions include increasing community awareness, ensuring sustainability of the program and establishing more treatment centers nationwide. Strategies such as reminders and patents' support will improve drug adherence among this cohort.

Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia.

WHAT IS KNOWN AND OBJECTIVE: Imatinib mesylate is the first-line drug for the treatment of Philadelphia/bcr-abl positive chronic myeloid leukaemia (CML). It is known to be metabolized mostly by CYP3A4 and CYP3A5 isoforms while its efflux is mediated by the transporters ABCB1 and ABCG2. Genetic polymorphism of some of these enzymes and transporters have been linked with inter-individual variations in the pharmacokinetics of the drug. This study, therefore, investigated the influence of CYP3A5*3, ABCG2 421C>A and ABCB1 3435 C>T genetic polymorphism on the clinical outcome and steady-state trough plasma concentration (TPC) of imatinib in Nigerians with CML. METHODS: A total of 110 Nigerians with CML each of whom had been receiving a 400 mg daily dose of imatinib for at least 1 month were genotyped for CYP3A5*3, ABCG2 421C>A and ABCB1 3435 C>T. The TPC of all the patients were determined by a validated HPLC method and possible relationships between genotypes, age, clinical outcome, sex, TPC and ethnicity were analysed. RESULTS AND DISCUSSION: Subjects of TT genotype of ABCB1 C3435T had higher frequencies of complete haematological response (CHR), complete cytogenetic response (CCR) and major molecular response (MMR) but these were not statistically significant (P < 0·05). No genetic polymorphism in ABCG2 421C>A was observed. However, significant associations were observed between TPC and various genotypes in both CYP3A5*3 (P < 0·001) and ABCB1 C3435T (P < 0·001). The GG and TT genotypes in CYP3A5*3 and ABCB1 C3435T, respectively, were linked with higher TPC. WHAT IS NEW AND CONCLUSION: This is the first pharmacogenetics study of CML patients in the Nigerian population with ethnic differences in the distribution of ABCB1 C3435T. Genetic polymorphisms in CYP3A5*3 and ABCB1 C3435T are associated with TPC in CML patients in this population.

Preliminary report of HLA (DNA) typing of Nigerians using sequence-specific primer technique.

AIMS AND OBJECTIVES: This communication is an attempt to present the experience and a preliminary report of results over a one-year period. PATIENTS AND METHODS: From December 2011 to December 2012, a prospective determination of the HLA types of 20 individuals referred to the Tissue Typing Laboratory of the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife was done. These consisted of prospective transplant recipients, their donors, and a migrant pair for kinship determination. DNA was extracted from the client's peripheral blood sample, using the QIAmp Blood DNA Mini kit, (Qiagen). PCR was done using OlerupR low-resolution PCR-SSP typing kit. The PCR product was resolved in 2% agarose gel, and the bands visualised under UV light. The HLA types were determined using provided tables and/or Helmberg software. Data were presented using descriptive statistics whileHLA antigen frequency (AF) was expressed in percentage and gene frequency (GF) was determined using square root method (1-(1-AF)1/2). RESULTS: A total of 20 individuals (13males and 7females) consisting of seven renal transplant recipients and seven prospective donors; a stem cell recipient and three donors and a migrant pair for kinship determination were typed. Age ranged from 4-65 years. 44 HLA alleles were detected, while HLA-A, B, C, DRB1 and DQB1 were 7, 10, 11, 8, 8 alleles respectively. The alleles were heterogeneous in distribution while 6 antigens (HLA-A*02, B*30, C*15, DRB1*03, DRB1*08 and DQB1*06) were having frequencies e"25%. CONCLUSION: This report confirms that DNA-based HLA typing is feasible locally, andit was observed that renal transplantation procedure is the most frequent indication. The HLA antigens observed to have very high frequencies (e"25% frequency) in this population were HLA-A*02, B*30, C*15, DRB1*03, DRB1*08 and DQB1*06. There is a strong need to develop a broad-based HLA data bank for Nigeria to further strengthening her transplantation programmes.

Imatinib (Glivec) and gastrointestinal stromal tumours in Nigerians.

BACKGROUND: To assess the response and the impact on the overall survival (OS) on c-KIT-positive (CD117+) gastrointestinal stromal tumours (GISTs) patients treated with imatinib mesylate. METHODS: Between July 2003 and December 2012, consenting patients with advanced c-kit-positive GISTs were enrolled to receive imatinib mesylate therapy at a dose of 400mg - 800mg daily, supplied gratis by Novartis Pharma (Basel, Switzerland) under its GIPAP initiative. Disease severity was based on tumour site, size and mitotic index at diagnosis. Clinical features together with drug toxicity, haematological and biochemical parameters were monitored. Overall survival (OS) reviewed at 12 months intervals over 5 years was computed using Kaplan-Meier RESULTS: There were 27 patients in all (17 males and 10 females with a median age of 52 years (range 26 - 83). Twenty three patients, 15 males and 8 females that have been followed up for at least 6 months were evaluated, aged 26-83 years (median = 56). There were 17 (73.9%) gastric tumours and 6 extragastric including 3 cases of peritoneum and 1 each of small gut, colon and rectum. At diagnosis, 21 (91.3%) cases were high risk, and 1 each fell into the intermediate and low risks, respectively. Ten patients (43.4%) including 5 with metastases presented with unresectable lesions. Five patients (21.7%) had complete tumour resection, 5 (3 with metastases) had partial resections and 3 others with non-bulky, nonmetastatic diseases underwent no surgery. Imatinib was used as the primary therapy for all patients, except the 5 patients that underwent complete tumour resection. Nine (39.1%) patients were lost to disease progression with a median survival of 16.7 +/- 10.7 (+/- SE) (95% CI = 0-37.6) months. The overall survival at 2 years for all patients was 71.9%, which dropped to 65.9% at 4 years. CONCLUSIONS: Although a small number of GISTs, imatinib induced an extended remission in patients with advanced disease, most of whom would have been dead within a few months of diagnosis.

Chronic lymphocytic leukaemia: a-twenty-years experience and problems in Ile-Ife, South-Western Nigeria.

AIM: To investigate the usefulness of some clinical and laboratory parameters in assessing the prognosis and survival of CLL in a resource-limited setting. METHODS: Between September 1986 and March 2007, 79 consecutive patients were retrospectively studied. Diagnosis was based on clinical and haematological findings. RESULTS: A total of 79 patients, aged 30 to 81 (median = 60) years were managed. There were 34 males and 45 females (ratio = 0.8:1). About 86.1% were aged above 50 years. Massive splenomegaly and hepatomegaly were recorded in 70.9% and 29.1% of patients, respectively. More than 63% presented in stage C. Anaemia was recorded in 74.7%. Haematocrit correlated negatively with WBC but positively with platelet count. The spleen correlated positively with liver. The overall survival at 2 years was 70.2%. Logistic regression showed that younger age, male sex, higher haematocrit, and lower platelet count improved survival, while lower WBC, moderate hepatomegaly and splenomegaly conferred survival advantage. CONCLUSION: It could be concluded that massive splenomegaly is a common finding in the majority of our patients. Non availability of immunophenotyping facility is a major constraint.

AIDS-related lymphomas in Nigeria

Aggressive non-Hodgkin's lymphoma (NHL), including primary central nervous system (CNS) lymphoma, lymphoblastic lymphoma and non-endemic Burkitt's lymphoma have been recognized as AIDS-defining cancers in most developed countries. However, HIV/AIDS epidemics appear not to have been associated with higher incidence of lymphomas in Africa. We therefore carried out this study to highlight the significance or otherwise of HIV/AIDS epidemics in the pathogenesis of lymphomas in a population of Nigerians with the disease. Since January 1993 to the present, all patients with haematologic cancers are routinely screened (following appropriate counseling) for HIV infection. Patients with a histological diagnosis of malignant chronic lymphoproliferative diseases {non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia (CLL), Burkitt's lymphoma (BL) and Hodgkin lymphoma (HL)} at the Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife from January 1993 to August 2008 were noted. Those patients confirmed to be HIV/AIDS positive among the cohort with lymphomas were retrospectively studied using their clinical case notes. Data obtained were analyzed using appropriate descriptive and inferential statistics. A total of 391 patients were histologically confirmed to have lymphoma {NHL-109, (27.9 percent); CLL-76, (19.4 percent); BL-178, (45.5 percent) and HL-28, (7.2 percent)} during the study period. Nine patients (2.3 percent) were confirmed to be HIV- positive, all within the age bracket 24-60 (median = 50) years. Six of these, five males and one female, ages 24-60 (median = 37.5) years, had NHL while another three, all females (age 50 - 68years; median = 56 years) had CLL. None of the patients with HL and BL were HIV positive. Patients with NHL presented at advanced stage of the disease (at least clinical stage IIIb), and all those with CLL presented at stage C of the International Working Party Classification. All the HIV-positive patients ...

Polycythaemia vera in Nigeria.

BACKGROUND: There is a paucity of reports on polycythaemia vera (PV) in Nigeria. The aim of this review is to present the pattern of clinical presentation, method of diagnosis, therapeutic options and treatment outcome in the face of limited facilities. MATERIALS AND METHODS: Case notes of patients with confirmed diagnosis of PV managed at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Nigeria from 1997 to 2006, were reviewed for clinical and laboratory parameters. The relative proportion of PV to other cases of haematologic cancers seen within the same period was determined. RESULTS: Seven patients, 5 males and 2 females, aged 42-70 years (median, 53 years) were studied. All the patients were symptomatic at diagnosis with the majority presenting with headaches, visual disturbances, and tinnitus. Clinical signs include conjuctival suffusion in all the patients; splenomegaly, hepatomegaly and hypertension in 3 patients (42.8%). Pruritus was uncommon (14.3%). One patient (14.3%) presented with fatal cerebrovacscular accident on admission. The average follow up period was 39.9 months, and 2 patients (28.6%) were followed up for more than 7years. Therapy consisted mainly of regular phlebotomy and low dose aspirin for suppression of thromboxane synthesis and control of thrombocytosis and erythomelalgia. PV accounts for just 0.03% of all the haematologic cancers seen. CONCLUSION: PV has a low incidence in our population and affects significantly the middle age persons. The clinical presentation consisted of headaches, visual disturbance, hypertension, and organomegaly. Treatment outcome are not different from those previously reported. The need for life-long follow up must be emphasised to patients at diagnosis.

AIDS-related lymphomas in Nigeria.

Aggressive non-Hodgkin's lymphoma (NHL), including primary central nervous system (CNS) lymphoma, lymphoblastic lymphoma and non-endemic Burkitt's lymphoma have been recognized as AIDS-defining cancers in most developed countries. However, HIV/AIDS epidemics appear not to have been associated with higher incidence of lymphomas in Africa. We therefore carried out this study to highlight the significance or otherwise of HIV/AIDS epidemics in the pathogenesis of lymphomas in a population of Nigerians with the disease. Since January 1993 to the present, all patients with haematologic cancers are routinely screened (following appropriate counseling) for HIV infection. Patients with a histological diagnosis of malignant chronic lymphoproliferative diseases {non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia (CLL), Burkitt's lymphoma (BL) and Hodgkin lymphoma (HL)} at the Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife from January 1993 to August 2008 were noted. Those patients confirmed to be HIV/AIDS positive among the cohort with lymphomas were retrospectively studied using their clinical case notes. Data obtained were analyzed using appropriate descriptive and inferential statistics. A total of 391 patients were histologically confirmed to have lymphoma {NHL-109, (27.9%); CLL-76, (19.4%); BL-178, (45.5%) and HL-28, (7.2%)} during the study period. Nine patients (2.3%) were confirmed to be HIV- positive, all within the age bracket 24-60 (median = 50) years. Six of these, five males and one female, ages 24-60 (median = 37.5) years, had NHL while another three, all females (age 50 - 68 years; median = 56 years) had CLL. None of the patients with HL and BL were HIV positive. Patients with NHL presented at advanced stage of the disease (at least clinical stage IIIb), and all those with CLL presented at stage C of the International Working Party Classification. All the HIV-positive patients with NHL succumbed to the disease within one to three weeks of admission into the hospital. The prevalence of AIDS-related lymphomas is 2.3% compared to 4.4% found in the general population. However, it is interesting that no single case of AIDS-associated BL was seen, despite the fact that Burkitt's lymphoma is endemic in this part of the world. All the patients presented at a very advanced stage of the disease with significantly shortened survival.